"Triarylphosphonium-conjugated Sn(IV)-porphyrins for Antimicrobial Photodynamic Therapy: Impact of Substituents on Lipophilicity, Aggregation, and Photoantibacterial Activity"

Abstract

Antimicrobial photodynamic therapy is an effecive approach to couteract bacterial infections that are not possible to be treated through antibiotics. In this study, three cationic Sn(IV) porphyrins bearing triaryl phosphonium substituents (SnP1, SnP2, and SnP3) were synthesized and evaluated as antibacterial photosensitizers (PS). All compounds exhibited efficient singlet oxygen generation with quantum yields (ΦΔ) in the range of 0.72-0.78. Aggregation studies shows reduced aggregation of SnP1 and SnP2 than SnP3. Lipophilicity (log P) values indicated that SnP2, containing fluoro substituents, possesses balanced amphilic character favorable for effective bacterial uptake and antimicrobial activity. The photodynamic antibacterial activity (427 nm LED, 22 mW cm−2) of SnP1, SnP2 and SnP3 was evaluated against Escherichia coli (E. coli) and clinical methicillin-resistant Staphylococcus aureus (MRSA). SnP2 exhibited significant photoantimicrobial activity against both gram negative (E. coli) and gram positive (MRSA) with log reduction of 8.7 at 10 µM and 8.4 at 20nM, respectively. Overall, our study highlights the importance of structural tuning of lipophilicity and aggregation in enhancing the efficacy of Sn(IV)-porphyrin based photosenstizers.